A conditionally lethal mutant of Salmonella Typhimurium induces a protective response in mice
| Autor: | Nicolás A. Villagra, Guido C. Mora, Sebastián A. Jerez, Juan A. Fuentes, Alejandro A. Hidalgo |
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| Rok vydání: | 2016 |
| Předmět: |
Salmonella typhimurium
0301 basic medicine Salmonella Normal diet Tetracycline 030106 microbiology Mutant Biophysics Administration Oral Spleen medicine.disease_cause Biochemistry Microbiology Mice 03 medical and health sciences Species Specificity medicine Animals Molecular Biology Mice Inbred BALB C biology Cell Biology biology.organism_classification In vitro Bacterial vaccine 030104 developmental biology medicine.anatomical_structure Salmonella enterica Bacterial Vaccines Mutation Salmonella Infections Female medicine.drug |
| Zdroj: | Biochemical and Biophysical Research Communications. 470:313-318 |
| ISSN: | 0006-291X |
| Popis: | Here we present the design of a conditionally lethal mutant of Salmonella enterica serovar Typhimurium (S. Typhimurium) which growth depends on tetracycline (Tet). Four mutants of S. Typhimurium, with Tet-conditional growth, were created by inserting the tetRA cassette. Three of the mutants presented a conditional-lethal phenotype in vitro. One mutant in the yabB gene remained conditional inside cells and did not persisted after 24 h in cell cultures. The capacity of S. Typhimurium yabB::tetRA to invade deep organs was investigated in intraperitoneally (IP) infected mice fed with or without chlortetracycline (CTet), a Tet analog with lower antibiotic activity. The yabB::tetRA mutant was undetectable in liver or spleen of animals under normal diet, while in mice under diet including CTet, yabB::tetRA invaded at a level comparable to the WT in mice under normal diet. Moreover, yabB::tetRA produced a strong humoral-immunoresponse after one IP immunization with 10(6) bacteria, measured as serum reactivity against S. Typhimurium whole cell extract. By contrast, oral immunization with 10(6) bacteria was weaker and variable on inducing antibodies. Consistently, IP infected mice were fully protected in a challenge with 10(4) oral S. Typhimurium, while protection was partial in orally immunized mice. Our data indicate that S. Typhimurium yabB::tetRA is a conditionally attenuated strain capable of inducing a protective response in mice in non-permissive conditions. |
| Databáze: | OpenAIRE |
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